ArticleDiabetes2013
Inhibition of Src kinase blocks high glucose-induced EGFR transactivation and collagen synthesis in mesangial cells and prevents diabetic nephropathy in mice.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 151 citations in OpenAlex.
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Lipoxin A4 activates Nrf2 expression and mitigates hyperglycaemia-induced impairment of myogenesis and rescues damage to mitochondria.Journal of physiology and biochemistry · 2026Article
- Network Pharmacology, Molecular Docking and Molecular Dynamics Studies to Predict the Molecular Targets and Mechanisms of Action ofPlants (Basel, Switzerland) · 2025Article
- Protective effects of Notoginsenoside R2 on reducing lipid accumulation and mitochondrial dysfunction in diabetic nephropathy through regulation of c-Src.Chinese medicine · 2025Article
- Acupuncture for diabetic nephropathy: mechanisms, clinical evidence, and future perspectives.Frontiers in endocrinology · 2025Review
- Article
- Src inhibition modulates AMBRA1-mediated mitophagy to counteract endothelial-to-mesenchymal transition in renal allograft fibrosis.Cell proliferation · 2024Article
- Metabolomic Profiling and Network Toxicology: Mechanistic Insights into Effect of Gossypol Acetate Isomers in Uterine Fibroids and Liver Injury.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions.MedComm · 2024Review
- Integrating serum pharmacochemistry and network pharmacology to explore potential compounds and mechanisms of Alpiniae oxyphyllae fructus in the treatment of cellular senescence in diabetic kidney disease.Frontiers in medicine · 2024Article
- Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels.Nature communications · 2023Article
- Podocarpusflavone alleviated renal fibrosis in obstructive nephropathy by inhibiting Fyn/Stat3 signaling pathway.Journal of natural medicines · 2023Article
- YY1-induced upregulation of LncRNA-ARAP1-AS2 and ARAP1 promotes diabetic kidney fibrosisFrontiers in pharmacology · 2023Article
- The Molecular Mechanism of Renal Tubulointerstitial Inflammation Promoting Diabetic Nephropathy.International journal of nephrology and renovascular disease · 2023Review
- Upregulation of the protein kinase Lyn is associated with renal injury in type 2 diabetes patients.Renal failure · 2023Article
- Bioinformatic prediction of the molecular links between Alzheimer's disease and diabetes mellitus.PeerJ · 2023Article
- Pan-Src kinase inhibitor treatment attenuates diabetic kidney injury via inhibition of Fyn kinase-mediated endoplasmic reticulum stress.Experimental & molecular medicine · 2022Article
- Src Family Kinases: A Potential Therapeutic Target for Acute Kidney Injury.Biomolecules · 2022Review
- Angiotensin II inhibits the A-type KAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2022Article
- γ Peptide Nucleic Acid-Based miR-122 Inhibition Rescues Vascular Endothelial Dysfunction in Mice Fed a High-Fat Diet.Journal of medicinal chemistry · 2022Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
Chronic exposure to high glucose leads to diabetic nephropathy characterized by increased mesangial matrix protein (e.g., collagen) accumulation. Altered cell signaling and gene expression accompanied by oxidative stress have been documented. The contribution of the tyrosine kinase, c-Src (Src), which is sensitive to oxidative stress, was examined. Cultured rat mesangial cells were exposed to high glucose (25 mmol/L) in the presence and absence of Src inhibitors (PP2, SU6656), Src small interfering RNA (siRNA), and the tumor necrosis factor-α-converting enzyme (TACE) inhibitor, TAPI-2. Src was investigated in vivo by administration of PP2 to streptozotocin (STZ)-induced diabetic DBA2/J mice. High glucose stimulated Src, TACE, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK1/2, p38), and collagen IV accumulation in mesangial cells. PP2 and SU6656 blocked high glucose-stimulated phosphorylation of Src Tyr-416, EGFR, and MAPKs. These inhibitors and Src knockdown by siRNA, as well as TAPI-2, also abrogated high glucose-induced phosphorylation of these targets and collagen IV accumulation. In STZ-diabetic mice, albuminuria, increased Src pTyr-416, TACE activation, ERK and EGFR phosphorylation, glomerular collagen accumulation, and podocyte loss were inhibited by PP2. These data indicate a role for Src in a high glucose-Src-TACE-heparin-binding epidermal growth factor-EGFR-MAPK-signaling pathway to collagen accumulation. Thus, Src may provide a novel therapeutic target for diabetic nephropathy.
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